Alterations In Functional Connectivity Of The Nac In Unilateral Mesial Temporal Lobe Epilepsy

ObjectiveThe nucleus accumbens plays a decisive role in both functional and anatomical connectivity between frontal and temporal lobes. In rodent models of temporal lobe seizures, the NAC has been shown to be involved in propagation of epileptic activity. The doctors in Department of Neurosurgery, Nanfang Hospital took the lead to stereotactic radiofrequency lesioning of nucleus accumbens in patients with bilateral temporal lobe epilepsy, also provided initial evidence for safety and feasibility of therapeutic efficacy.However little is known about the role of NAc at network level in patients with TLE. To investigate alterations in functional connectivity of the NAc in unilateral mesial temporal lobe epilepsy, we performed functional connection technology based on resting state fMRI to assessed the alterations of the functional connectivity using resting-state fMRI based on brain seed-region analysis approachMaterials and methodsThe study was conducted in the Department of Diagnostic Imaging Center, Nanfang Hospital, Guangzhou, China, from May2013to Apirl2014. Patients diagnosed with mesial temporal lobe epilepsy and admitted to the indoor Department of Neurology, were enrolled in the study. All patients underwent presurgical inpatient video-electroencephalography (EEG) monitoring for localization of the epileptogenic zone, high-resolution structural MRI, fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological testing. Inclusion criteria for this study were the following:(1) seizure types and epileptic syndromes as diagnosed according to the classification of the International League Against Epilepsy (Berg et al.,2010),(2) TLE diagnosis when continuous interictal-ictal scalp video electroencephalography showed interical epileptiform discharges (IEDs) of unilateral temporal origin,(3) FDG-PET showed unilateral mesial temporal lobe hypometabolism in accordance with the lateralization demonstrated by EEG,(4) temporal resection as epilepsy surgery,(5) postoperative pathological diagnoses were hippocampal sclerious,(6) Chineses, right-handed. Finally, a total of24subjects with unilateral mTLE were included in this study (11patients with left TLE, three female and eight male, mean age22.24±6.38years; and13patients with right TLE, three female and ten male, mean age25.36±8.23years). In addition, we recruited24right-handed healthy control subjects for comparison (15female and9male, mean age25.67±2.58years). There is no statistically significant difference in age between the right TLE (n=13), left TLE (n=11), and control (n=24) groups. Similarly, mere was no statistical difference in duration of disease between the right and left TLE groups.All MRI imaging was performed on a Philips Achieva3T MRI scanner (Philips Healthcare, Inc., Best, The Netherlands) using an8-channel head coil. The imaging sequences included:(1) three-dimensional (3D) T1-weighted highresolution image series across the whole brain for intersubject normalization,(2) fMRI blood oxygenation level dependent (BOLD) image series at rest with eyes closed. (3)conventional axial T2WI, T1WI and FLAIR series.Data preprocessing was partly carried out using SPM8software based on Matlab R2010. The reprocessing as follows:(1) Data with DICOM format were converted to NIFTI format;(2) The first10images were discarded to ensure the magnetization equilibrium;(3) Then the remaining images were realigned, the subjects would be excluded for head translation or rotation exceeded±1mm or±1°;(4) Slice timing, correct differences in image acquisition time between slices;(5)Normalization, normalize images into a standard Talairach and Tournoux space by MNI template images which supplied with SPM8;(6) The images were proceed with linear detrend and low-frequency filtering, then the preprocessed time series were used for further functional connectivity analysis. We used bilateral NAc as seed ROIs performed by FSL and functional connectivity was analyzed based on resting-state fMRI data in order to determine the temporal correlation between bilateral accumbens and the other regions on the whole brain scale by Statistical Parametric Mapping (SPM). Finally, one-sample t-test and two-sample t-test were applied to determine the alterations of functional connectivity pattern of NAc in mTLE patients (P=0.01, cluster size=15voxels).Results1. Left mTLE groups compared to control group, showed decreased functional connectivity between left NAc and bilateral thalamus, right putamen, posterior cingutate cortex, precuneus, but did not show any increased functional connectivity with left NAc.2. Left mTLE groups compared to control group, showed decreased functional connectivity between right NAc and vermis, posterior cingutate cortex, precuneus, bilateral angular gyrus, left frontal middle gyrus and so on, but did not show any increased functional connectivity with right NAc. 3. Right mTLE groups compared to control group, showed decreased functional connectivity between left NAc and vermis, bilateral thalamus, right parahippocampus, right orbitofrontal cortex, left frontal middle gyrus, but did not show any increased functional connectivity with left NAc.4. Right mTLE groups compared to control group, showed decreased functional connectivity between right NAc and vermis, left orbitofrontal cortex and mesial prefrontal cortex, left brainstem, bilateral angular gyrus, but did not show any increased functional connectivity with right NAc.5. Among left mTLE patiens, the functional connectivity between right NAc and left frontal gyrus appeared to show a negative correlation with SAS scores; while among right mTLE patients, the funtional connectivity between right NAc and left brainstem showed a positive correlation with epilepsy duration.Conclusion1. It showed that extensive decreased functional connectivity of bilateral NAc in mTLE patients, suggest that the NAc may paly an important role in epileptic networks.2. The functional connectivity between right NAc and left frontal gyrus showed a negative correlation with SAS scores which seems to reflect some of the pathophysiologic substrate of anxiety in mTLE patients.3. The between right NAc and left brainstem showed a positive correlation with epilepsy duration in mTLE, suggest a rebuilding of the aberrant decreased funtional connectivity in epileptic networks.